Perinatal and 2-year neurodevelopmental outcome in late preterm fetal: the TRUFFLE 2 randomised trial protocolcompromise

TY - JOUR

T1 - Perinatal and 2-year neurodevelopmental outcome in late preterm fetal: the TRUFFLE 2 randomised trial protocolcompromise

AU - Mylrea-Foley, Bronacha

AU - Thornton, Jim G

AU - Mullins, Edward

AU - Marlow, Neil

AU - Hecher, Kurt

AU - Ammari, Christina

AU - Arabin, Birgit

AU - Berger, Astrid

AU - Bergman, Eva

AU - Bhide, Amarnath

AU - Bilardo, Caterina

AU - Binder, Julia

AU - Breeze, Andrew

AU - Brodszki, Jana

AU - Calda, Pavel

AU - Cannings-John, Rebecca

AU - Černý, Andrej

AU - Cesari, Elena

AU - Cetin, Irene

AU - Dall'Asta, Andrea

AU - Diemert, Anke

AU - Ebbing, Cathrine

AU - Eggebø, Torbjørn

AU - Fantasia, Ilaria

AU - Ferrazzi, Enrico

AU - Frusca, Tiziana

AU - Ghi, Tullio

AU - Goodier, Jenny

AU - Greimel, Patrick

AU - Gyselaers, Wilfried

AU - Hassan, Wassim

AU - Von Kaisenberg, Constantin

AU - Kholin, Alexey

AU - Klaritsch, Philipp

AU - Krofta, Ladislav

AU - Lindgren, Peter

AU - Lobmaier, Silvia

AU - Marsal, Karel

AU - Maruotti, Giuseppe M

AU - Mecacci, Federico

AU - Myklestad, Kirsti

AU - Napolitano, Raffaele

AU - Ostermayer, Eva

AU - Papageorghiou, Aris

AU - Potter, Claire

AU - Prefumo, Federico

AU - Raio, Luigi

AU - Richter, Jute

AU - Sande, Ragnar Kvie

AU - Schlembach, Dietmar

AU - Schleußner, Ekkehard

AU - Stampalija, Tamara

AU - Thilaganathan, Basky

AU - Townson, Julia

AU - Valensise, Herbert

AU - Visser, Gerard Ha

AU - Wee, Ling

AU - Wolf, Hans

AU - Lees, Christoph C

AU - Truffle-2 Group

N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

PY - 2022/4/15

Y1 - 2022/4/15

N2 - INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

AB - INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

KW - Cardiotocography

KW - Child

KW - Female

KW - Fetal Growth Retardation

KW - Fetal Weight

KW - Heart Rate, Fetal/physiology

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Pregnancy

KW - Premature Birth

KW - Randomized Controlled Trials as Topic

KW - Ultrasonography, Prenatal

U2 - 10.1136/bmjopen-2021-055543

DO - 10.1136/bmjopen-2021-055543

M3 - SCORING: Journal article

C2 - 35428631

VL - 12

JO - BMJ OPEN

JF - BMJ OPEN

SN - 2044-6055

IS - 4

M1 - e055543

ER -